Air pollution and placental function

Abstract

Maternal exposure to air pollution during pregnancy had been associated with adverse pregnancy outcomes, such as pre-eclampsia and fetal growth restriction (FGR), but the mechanism of this effect is poorly understood. Particulate matter (PM) is a ubiquitous air pollutant that is present both the indoor and outdoor environment and potentially bound with toxic materials such as heavy metals and/or polycyclic aromatic hydrocarbons (PAHs). Placental explant culture offers an in-vitro means to study PM induced changes in placental endocrine function and cellular turnover. This PhD explores the possible routes of air pollutant exposure and their mechanism influences on placental dysfunction that can cause adverse pregnancy outcomes. Placentas were collected following elective caesarean section (ELCS) at-term, between October 2017 and January 2019 at St. Mary’s Hospital, Manchester, and 41 villous explants were established, but 12 were excluded, as 4 were contaminated and 8 were non-responsive. Initially, placental explants were exposed to diesel exhaust particles (DEP) for 48-hour from day 5 until 7 of culture, to determine if there was a short term effect of this air pollutant on hCG secretion, and the result showed that 48-hour treatment were not give a significant changed in hCG secretion between treated and control group. Informed with the short term effect, the duration of air pollutants treatment on explants in culture was extended over 6 days. Explants were treated with DEP and house dust (HD), to mimic maternal exposure to PM2.5 bound PAH. DEP treatment (SRM1650b; 24-hours/day; 6-days/week; mean DEP diameter ~166nm) significantly increased hCG secretion, increased 8-OHdG oxidative damage and promoted the formation of villi with an intact syncytiotrophoblast in a dose-dependent manner, whereas HD (SRM2585; 24-hours/day; 6-days/week; mean HD diameter ~166nm) significantly inhibited hCG secretion, increased the number of shed villi without regeneration and increased 8-OHdG oxidative damage. Differences in PAH levels between DEP and HD may be a reason for the difference in hCG secretion response and cellular turnover by placental explants. Analysis of PAH and heavy metal levels in placentas and maternal blood has been conducted to indicate the functional ability of the placenta to act as a protective barrier for the fetus. Placentas and maternal blood from 53 patients were collected between June 2015 and June 2017 at St. Mary’s Hospital, Manchester. Heavy metals, as detected by an inductive coupled mass spectrometer (ICP-MS), were present in the majority of samples, except for Cr and Ni which not detected in maternal blood. Cu and Pb levels were higher in maternal blood, whereas Cd and Hg levels were higher in placenta samples. PAH levels, as determined by gas chromatography with mass spectrometric (GC-MS), were low in placental samples, with only 8 out of 12 samples containing detectable levels, and most of the positive samples (n=5/8) contained only one PAH. Amongst 10 PAH compounds, fluorene, fluoranthene and pyrene detected in 8, 3 and 3 samples, respectively, whereas other compounds were detected in only one sample. Low maternal exposure on ambient PM10 and PM2.5 levels throughout the gestation period, with median (IQR) levels of 17.6 (16.6 – 17.9)µg/m3 and 10.1 (9.3 – 10.8)µg/m3 respectively, as determined by air pollution monitoring stations, may be a reason for low heavy metal and PAH levels in the biological samples. The investigation of maternal exposure to air pollution extended with a feasibility study of indoor air particle measurement in 20 residential homes of pregnant women across Greater Manchester (GM), between February and August 2019. The majority (n=17/20) of residential homes contained indoor PM2.5 levels below 20µg/m3, as measured by an air particle monitor (DYLOS DC1700) for 24-hour. Simultaneously, outdoor PM2.5 levels were estimated from air pollution monitoring stations, and the results show

Date of Award	31 Dec 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Andrew Povey (Supervisor) & Edward Johnstone (Supervisor)